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MOLECULAR BIOLOGY – Basic Genetics
MOLECULAR BIOLOGY AND GENETICS
1. Genetic basis2. DNA structure and genetic code3. Cell division, replication and transcription4. RNA processing 5. Regulation of gene expression6. Translation, function of proteins7. DNA variation – mutations and repair8. Recombinant DNA9. PCR, sequencing, genomics10.Gene expression analysis11.Protein analysis, proteomics
MOLECULAR BIOLOGY – Basic Genetics
GENETIC BASIS OF LIFE
MOLECULAR BIOLOGY – Basic Genetics
CENTRAL PROPOSITION OF EVOLUTION
All living forms origin in common ancestors, they can change and give rise to new species.
1. Closely related species share common ancestor
2. Natural selection is a mechanism for evolution
2 major concepts:
November 24th, 1859:
Darwin Wallace
MOLECULAR BIOLOGY – Basic Genetics
new questions:
1. More progeny is born and some characters (advantageous) are more likely to be passed to the next generation.
HOW ARE THE CHARACTERS INHERITED?
2. There has to be variability in populations so thatthe natural selection has the pool to select from.
WHAT IS THE SOURCE OF VARIABILITY?
THEORY OF EVOLUTION
Augustinian monastery in Brno
Johann Gregor Mendel(*1822 - †1884)
MOLECULAR BIOLOGY – Basic Genetics
Mendel picked 7 characters which existed in 2 forms:
MOLECULAR BIOLOGY – Basic Genetics
He made „true-breeding varieties“ all individuals present in one form or the other for number of generations
Carpel
Anthers
MOLECULAR BIOLOGY – Basic Genetics
Pollen
amputated anthers
F1
F2
P
MOLECULAR BIOLOGY – Basic Genetics
Mendel: 5 474 1 850
MOLECULAR BIOLOGY – Basic Genetics
Mendel’s first experiment
Mendel’s interpretation of his results
1. Each form of a character is controlled by certain heritable factor
2. Obtained results are best explained by the existence of factors in pair
3. Each parent passes to progeny only one of its two factors for the character
MAIN CONCEPT OF HEREDITY arising from Mendel’s work
relationship between gene and allele
CHARACTER = GENEFACTOR = ALLELE = certain form of character
MOLECULAR BIOLOGY – Basic Genetics
DOMINANT and RECESSIVEfactors (alleles)
HOMOZYGOTES and HETEROZYGOTES
GENOTYPE and PHENOTYPE
1:2:1 3:1
Random segregation of alleles
MOLECULAR BIOLOGY – Basic Genetics
MOLECULAR BIOLOGY – Basic Genetics
For Mendel genes were just a theoretical entity
What is a physical essence of the inherited factors?
How are they copied, transmitted and expressed?
Zell-substanz, Kern und Zelltheilung (1882)
Walther Flemming
MOLECULAR BIOLOGY – Basic Genetics
1. Chromosomes show specific forms and sizes2. Number of chromosomes is characteristic for each species3. In most plants and animals chromosomes were present
in pairs
in agreement with Mendel’s observation about heredity
INTEGRATION OF CYTOLOGY AND GENETICS - CYTOGENETICS
1902-1903 four cytogeneticists independently formulated a concept:„Mendel’s laws of inheritance are direct consequences of organization and behavior of chromosomes“
MOLECULAR BIOLOGY – Basic Genetics
PROBLEMS TO ACCEPT CHROMOSOME THEORY OF INHERITANCE
It was obvious that there is more genes than chromosomes.
How is then possible that the genes do not „travel“ with chromosomes? (Mendel was lucky to pick each factor on different chromosome)
Nobody observed that a certain gene would travel from generation to generation together with certain chromosome.
MOLECULAR BIOLOGY – Basic Genetics
Thomas Hunt Morgan(1866-1945)
Drosophila melanogaster
1910
MOLECULAR BIOLOGY – Basic Genetics
X
X
P
F1
F2
X XY X
Y X X X
X X X XY XY X
MOLECULAR BIOLOGY – Basic Genetics
yellow white miniature
MOLECULAR BIOLOGY – Basic Genetics
MOLECULAR BIOLOGY – Basic Genetics
FIRST SUMMARY – CRUCIAL KNOWLEDGE
allele X1 allele X2
protein X1 protein X2
nucleus
cytoplasmGene X in diploid cell
Pair of homologous chromosomes, one from father, one from mother
MOLECULAR BIOLOGY – Basic Genetics
Somatic lineMitosisGenetic information is not mixed
both progeny cells are geneticallythe same as the parental cell
MOLECULAR BIOLOGY – Basic Genetics
grandfather Agrandmother A
MOTHER FATHER
from grandfather B
from grandfather Bfrom grandfather A
from grandmother A
Recombinationbetween pairsof homologouschromosomes
MOLECULAR BIOLOGY – Basic Genetics
grandfather Bgrandmother B
GENES ARE ON CHROMOSOMES
proteins
DNA
MOLECULAR BIOLOGY – Basic Genetics
Frederick Griffith (1871 - 1941)
MOLECULAR BIOLOGY – Basic Genetics
1928 – Griffith’s experiment
TRANSFORMATION OF GENETIC MATERIAL
MOLECULAR BIOLOGY – Basic Genetics
Oswald T. Avery Colin M. MacLeod Maclyn McCarty
1944
What was the transformation factor?What was the transformation factor?
Rockefeller Institute for Medical Research, New York
MOLECULAR BIOLOGY – Basic Genetics
TRANSFORMATION FACTOR
MOLECULAR BIOLOGY – Basic Genetics
Bacteriophage infecting E.coli
MOLECULAR BIOLOGY – Basic Genetics
Martha Chase a Alfred Hershey - 1952
MOLECULAR BIOLOGY – Basic Genetics
DNA Methionin
32P
35S
35S
32P
32P32P
32P
MOLECULAR BIOLOGY – Basic Genetics
Hershey-Chase experiment
MOLECULAR BIOLOGY – Basic Genetics
MOLECULAR BIOLOGY – Basic Genetics